Konieczko K M, Jones J G, Barrowcliffe M P, Jordan C, Altman D G
Division of Anaesthesia, Northwick Park Hospital, Harrow, Middx.
Br J Anaesth. 1988 Sep;61(3):318-23. doi: 10.1093/bja/61.3.318.
The duration of respiratory depression induced by morphine 10 mg/70 kg was studied following the administration of one of two opioid antagonists. Respiratory measurements included: (i) the ventilatory response to carbon dioxide, described in two ways--the minute ventilation at an end-tidal carbon dioxide partial pressure of 8 kPa (VE8) and the log slope of the ventilatory response to carbon dioxide; (ii) resting end-tidal carbon dioxide partial pressure; (iii) rate of ventilation. One hour after administration of morphine, one of the following was given i.v.: nalmefene 0.4 mg/70 kg; naloxone 0.4 mg/70 kg (low dose); naloxone 1.6 mg/70 kg (high dose); or saline placebo. The depression of VE8 by morphine was antagonized by all three treatments for the 1.5 h after the injection. However, for the 1.5-6 h after antagonist, VE8 following naloxone became depressed, whereas VE8 after nalmefene remained significantly increased compared with other treatments. Nalmefene restored the slope of the ventilatory response to baseline for 6 h and differed significantly from low but not high dose naloxone. Resting end-tidal carbon dioxide measurements demonstrated that nalmefene activity exceeded that of low but not high dose naloxone over the 1.5-4.5 h period. Rate of ventilation was not different between treatments.
在给予两种阿片类拮抗剂之一后，研究了10mg/70kg吗啡诱导的呼吸抑制持续时间。呼吸测量包括：（i）对二氧化碳的通气反应，用两种方式描述——呼气末二氧化碳分压为8kPa时的分钟通气量（VE8）以及对二氧化碳通气反应的对数斜率；（ii）静息呼气末二氧化碳分压；（iii）通气频率。给予吗啡1小时后，静脉注射以下药物之一：纳美芬0.4mg/70kg；纳洛酮0.4mg/70kg（低剂量）；纳洛酮1.6mg/70kg（高剂量）；或生理盐水安慰剂。注射后1.5小时内，所有三种治疗均拮抗了吗啡对VE8的抑制作用。然而，在给予拮抗剂后的1.5 - 6小时内，纳洛酮后的VE8出现下降，而与其他治疗相比，纳美芬后的VE8仍显著升高。纳美芬在6小时内将通气反应斜率恢复至基线，且与低剂量但非高剂量纳洛酮有显著差异。静息呼气末二氧化碳测量结果表明，在1.5 - 4.5小时期间，纳美芬的活性超过低剂量但不超过高剂量纳洛酮。各治疗组之间的通气频率无差异。
